Cynanchum paniculatum (Bunge) Kitag. ex H.Hara inhibits pancreatic cancer progression by inducing caspase-dependent apoptosis and suppressing TGF-β-mediated epithelial-mesenchymal transition.

Autor:	Cheng CS; Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China.; Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Wu Y; Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China., Jin JB; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Xu JY; Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China., Yang PW; Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Zhu WH; Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China., Zheng L; Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China., Chen JX; Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2024 May 31; Vol. 15, pp. 1284371. Date of Electronic Publication: 2024 May 31 (Print Publication: 2024).
DOI:	10.3389/fphar.2024.1284371
Abstrakt:	Background: Cynanchum paniculatum (Bunge) Kitag. ex H.Hara, a member of the Asclepiadaceae family, has a rich history as a traditional Chinese medicinal plant used to treat digestive disorders. However, its potential anti-cancer effects in pancreatic cancer remain largely unexplored. Aim: This study delves into the intricate anti-pancreatic cancer mechanisms of C. paniculatum (Bunge) Kitag. ex H.Hara aqueous extract (CPAE) by elucidating its role in apoptosis induction and the inhibition of invasion and migration. Methods: A comprehensive set of methodologies was employed to assess CPAE's impact, including cell viability analyses using MTT and colony formation assays, flow cytometry for cell cycle distribution and apoptosis assessment, scratch-wound and Matrigel invasion assays for migration and invasion capabilities, and immunoblotting to measure the expression levels of key proteins involved in apoptosis and metastasis. Additionally, a murine xenograft model was established to investigate CPAE's in vivo anti-cancer potential. Results: CPAE exhibited time- and dose-dependent suppression of proliferation and colony formation in pancreatic cancer cells. Notably, CPAE induced apoptosis and G2/M phase arrest, effectively activating the caspase-dependent PARP pathway. At non-cytotoxic doses, CPAE significantly curtailed the metastatic abilities of pancreatic cells, effectively suppressing epithelial-mesenchymal transition (EMT) and downregulating the TGF-β1/Smad2/3 pathway. In vivo experiments underscored CPAE's ability to inhibit tumor proliferation. Conclusion: This study illuminates the multifaceted anti-proliferative, pro-apoptotic, anti-invasive, and anti-migratory effects of CPAE, both in vitro and in vivo . CPAE emerges as a promising herbal medicine for pancreatic cancer treatment, with its potential mediated through apoptosis induction via the caspase-dependent PARP pathway and MET suppression via the TGF-β1/Smad2/3 signaling pathway at non-cytotoxic doses. These findings advocate for further exploration of CPAE's therapeutic potential in pancreatic cancer. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Cheng, Wu, Jin, Xu, Yang, Zhu, Zheng and Chen.)
Databáze:	MEDLINE
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